Liposomes were prepared to incorporate large amounts of amphotericin B. BALB/c mice were challenged with Cryptococcus neoformans and given liposome-associated amphotericin B (AMBL) or amphotericin B-deoxycholate (AMBD) intravenously. Mice that were treated with AMBL survived longer and had lower tissue counts of cryptococci than mice treated with AMBD or untreated control mice. The reduced acute toxicity of AMBL permitted much larger doses of amphotericin B to be given than were possible with AMBD. AMBL is a novel vehicle of administration that reduces toxicity and concentrates the drug in the appropriate target organs.
Cationic liposomes composed of sphingomyelin, cholesterol, and stearylamine were prepared with horseradish peroxidase trapped inside. Stable particles were formed in which 10-12% of the enzymic activity appeared to be located at, or near, the outer surface of the liposome. Adsorption and uptake of liposomes by HeLa cells were followed cytochemically by electron microscopy and quantitated by enzyme assay and by the distribution and fate of particles labeled with [t4C]cholesterol and [lZSI]horseradish peroxidase. The particles were adsorbed by HeLa cells at least 300 times as efficiently as was free horseradish peroxidase. Many of the particles remained at the cell surface, but numerous membrane-bound cytoplasmic inclusions were observed to contain peroxidase-staining material. In addition, many areas of the cell membrane gave a positive staining reaction. It was concluded that many particles (presumably the larger ones) did not gain access to the interior of the cells, many were phagocytized, and some enzyme was transferred to the cell membrane, perhaps as a result of fusion of the liposomal membrane with the cell membrane.
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